ID TYTR_CRIFA Reviewed; 491 AA.
AC P39040;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-APR-2013, entry version 98.
DE RecName: Full=Trypanothione reductase;
DE Short=TR;
DE EC=1.8.1.12;
DE AltName: Full=N(1),N(8)-bis(glutathionyl)spermidine reductase;
GN Name=TPR;
OS Crithidia fasciculata.
OC Eukaryota; Euglenozoa; Kinetoplastida; Trypanosomatidae;
OC Leishmaniinae; Crithidia.
OX NCBI_TaxID=5656;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1453951; DOI=10.1111/j.1365-2958.1992.tb01766.x;
RA Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT "Molecular characterization of the trypanothione reductase gene from
RT Crithidia fasciculata and Trypanosoma brucei: comparison with other
RT flavoprotein disulphide oxidoreductases with respect to substrate
RT specificity and catalytic mechanism.";
RL Mol. Microbiol. 6:3089-3099(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=1542316; DOI=10.1016/0166-6851(92)90243-D;
RA Field H., Cerami A., Henderson G.B.;
RT "Cloning, sequencing, and demonstration of polymorphism in
RT trypanothione reductase from Crithidia fasciculata.";
RL Mol. Biochem. Parasitol. 50:47-56(1992).
RN [3]
RP PROTEIN SEQUENCE OF 39-62, AND CHARACTERIZATION.
RX PubMed=3718941; DOI=10.1021/bi00360a007;
RA Shames S.L., Fairlamb A.H., Cerami A., Walsh C.T.;
RT "Purification and characterization of trypanothione reductase from
RT Crithidia fasciculata, a newly discovered member of the family of
RT disulfide-containing flavoprotein reductases.";
RL Biochemistry 25:3519-3526(1986).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND DISULFIDE BOND.
RX PubMed=8477734; DOI=10.1111/j.1432-1033.1993.tb17734.x;
RA Bailey S., Smith K., Fairlamb A.H., Hunter W.N.;
RT "Substrate interactions between trypanothione reductase and N1-
RT glutathionylspermidine disulphide at 0.28-nm resolution.";
RL Eur. J. Biochem. 213:67-75(1993).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=1522596; DOI=10.1016/0022-2836(92)90701-K;
RA Hunter W.N., Bailey S., Habash J., Harrop S.J., Helliwell J.R.,
RA Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT "Active site of trypanothione reductase. A target for rational drug
RT design.";
RL J. Mol. Biol. 227:322-333(1992).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=15299452; DOI=10.1107/S0907444993011898;
RA Bailey S., Fairlamb A.H., Hunter W.N.;
RT "Structure of trypanothione reductase from Crithidia fasciculata at
RT 2.6-A resolution; enzyme-NADP interactions at 2.8-A resolution.";
RL Acta Crystallogr. D 50:139-154(1994).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
RX PubMed=15299300; DOI=10.1107/S0907444994010772;
RA Strickland C.L., Puchalski R., Savvides S.N., Karplus P.A.;
RT "Overexpression of Crithidia fasciculata trypanothione reductase and
RT crystallization using a novel geometry.";
RL Acta Crystallogr. D 51:337-341(1995).
CC -!- FUNCTION: Trypanothione is the parasite analog of glutathione;
CC this enzyme is the equivalent of glutathione reductase.
CC -!- CATALYTIC ACTIVITY: Trypanothione + NADP(+) = trypanothione
CC disulfide + NADPH.
CC -!- COFACTOR: Binds 1 FAD per subunit.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-8.0;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: The N-terminus is blocked.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family.
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DR EMBL; Z12618; CAA78264.1; -; Genomic_DNA.
DR EMBL; M73323; AAA30321.1; -; mRNA.
DR EMBL; M73324; AAA30322.1; -; Genomic_DNA.
DR EMBL; M73325; AAA30323.1; -; Genomic_DNA.
DR PIR; S28002; S28002.
DR PDB; 1FEA; X-ray; 2.20 A; A/B/C/D=2-491.
DR PDB; 1FEB; X-ray; 2.00 A; A/B=2-491.
DR PDB; 1FEC; X-ray; 1.70 A; A/B=2-491.
DR PDB; 1TYP; X-ray; 2.80 A; A/B=1-487.
DR PDB; 1TYT; X-ray; 2.60 A; A/B=1-487.
DR PDB; 2TPR; X-ray; 2.40 A; A/B=2-491.
DR PDBsum; 1FEA; -.
DR PDBsum; 1FEB; -.
DR PDBsum; 1FEC; -.
DR PDBsum; 1TYP; -.
DR PDBsum; 1TYT; -.
DR PDBsum; 2TPR; -.
DR ProteinModelPortal; P39040; -.
DR SMR; P39040; 1-487.
DR BioCyc; MetaCyc:MONOMER-13293; -.
DR BindingDB; P39040; -.
DR ChEMBL; CHEMBL5394; -.
DR EvolutionaryTrace; P39040; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0015036; F:disulfide oxidoreductase activity; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0015042; F:trypanothione-disulfide reductase activity; IEA:EC.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR Gene3D; 3.30.390.30; -; 1.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer.
DR InterPro; IPR013027; FAD_pyr_nucl-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR023753; Pyr_nucl-diS_OxRdtase_FAD/NAD.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR InterPro; IPR001327; Pyr_OxRdtase_NAD-bd_dom.
DR InterPro; IPR001864; Trypnth_redctse.
DR Pfam; PF00070; Pyr_redox; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PRINTS; PR00368; FADPNR.
DR PRINTS; PR00470; TRYPANRDTASE.
DR SUPFAM; SSF55424; FAD/NAD-linked_reductase_dimer; 1.
DR TIGRFAMs; TIGR01423; trypano_reduc; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW FAD; Flavoprotein; NADP; Oxidoreductase; Redox-active center.
FT CHAIN 1 491 Trypanothione reductase.
FT /FTId=PRO_0000067988.
FT NP_BIND 35 51 FAD.
FT ACT_SITE 461 461 Proton acceptor.
FT DISULFID 52 57 Redox-active.
FT VARIANT 479 479 Q -> E.
FT CONFLICT 16 16 G -> R (in Ref. 2; AAA30322/AAA30323).
FT CONFLICT 62 62 L -> Y (in Ref. 3; AA sequence).
FT CONFLICT 297 297 D -> E (in Ref. 2; AAA30321/AAA30322/
FT AAA30323).
FT CONFLICT 454 454 F -> V (in Ref. 2; AAA30322/AAA30323).
FT STRAND 4 10
FT HELIX 14 27
FT STRAND 31 36
FT STRAND 38 41
FT TURN 42 44
FT HELIX 51 55
FT HELIX 57 75
FT HELIX 76 79
FT HELIX 85 87
FT HELIX 92 115
FT STRAND 120 131
FT STRAND 134 142
FT STRAND 147 158
FT STRAND 162 164
FT HELIX 172 174
FT HELIX 178 181
FT STRAND 189 194
FT HELIX 198 210
FT STRAND 216 227
FT HELIX 232 244
FT STRAND 247 251
FT STRAND 255 260
FT STRAND 266 270
FT STRAND 275 283
FT STRAND 287 290
FT HELIX 292 294
FT HELIX 296 299
FT STRAND 322 324
FT HELIX 326 329
FT HELIX 335 350
FT STRAND 364 366
FT STRAND 368 370
FT STRAND 372 376
FT HELIX 379 385
FT STRAND 387 396
FT HELIX 399 404
FT STRAND 411 418
FT TURN 419 421
FT STRAND 423 431
FT HELIX 434 446
FT HELIX 451 455
FT HELIX 465 469
FT STRAND 475 479
FT STRAND 482 484
SQ SEQUENCE 491 AA; 53229 MW; EF749215A16F9187 CRC64;
MSRAYDLVVI GAGSGGLEAG WNAASLHKKR VAVIDLQKHH GPPHYAALGG TCVNVGCVPK
KLMVTGANYM DTIRESAGFG WELDRESVRP NWKALIAAKN KAVSGINDSY EGMFADTEGL
TFHQGFGALQ DNHTVLVRES ADPNSAVLET LDTEYILLAT GSWPQHLGIE GDDLCITSNE
AFYLDEAPKR ALCVGGGYIS IEFAGIFNAY KARGGQVDLA YRGDMILRGF DSELRKQLTE
QLRANGINVR THENPAKVTK NADGTRHVVF ESGAEADYDV VMLAIGRVPR SQTLQLDKAG
VEVAKNGAIK VDAYSKTNVD NIYAIGDVTD RVMLTPVAIN EGAAFVDTVF ANKPRATDHT
KVACAVFSIP PMGVCGYVEE DAAKKYDQVA VYESSFTPLM HNISGSTYKK FMVRIVTNHA
DGEVLGVHML GDSSPEIIQS VAICLKMGAK ISDFYNTIGV HPTSAEELCS MRTPAYFYQK
GKRVEKIDSN L
//
